期刊
GENES & DEVELOPMENT
卷 27, 期 13, 页码 1435-1440出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.220202.113
关键词
B cells; prostate; regeneration
资金
- AICF
- Department of Defense Congressionally Directed Medical Research Programs
- American Cancer Society
- German Research Foundation (Deutsche Forschungsgemeinschaft) [SH721/1-1]
- Nation Cancer Institute [T32CA121938]
- NIH Pathway to Independence award [K99/R00 CA158055-01]
- NIH [CA127923]
Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate I kappa B kinase a (IKK alpha) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKK alpha are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKK alpha phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKK alpha-BMI1 pathway is also activated in human PCa.
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